US6566350B2 - Minocycline-containing compositions - Google Patents

Minocycline-containing compositions Download PDF

Info

Publication number
US6566350B2
US6566350B2 US09/860,503 US86050301A US6566350B2 US 6566350 B2 US6566350 B2 US 6566350B2 US 86050301 A US86050301 A US 86050301A US 6566350 B2 US6566350 B2 US 6566350B2
Authority
US
United States
Prior art keywords
weight
minocycline
pharmaceutical composition
fatty acid
oleaginous base
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US09/860,503
Other versions
US20020002151A1 (en
Inventor
Kazuhiro Ono
Hidenari Sakaguchi
Ikuto Hayakawa
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Showa Yakuhin Kako Co Ltd
Original Assignee
Showa Yakuhin Kako Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Showa Yakuhin Kako Co Ltd filed Critical Showa Yakuhin Kako Co Ltd
Assigned to SHOWA YAKUHIN KAKO CO., LTD. reassignment SHOWA YAKUHIN KAKO CO., LTD. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: HAYAKAWA, IKUTO, ONO, KAZUHIRO, SAKAGUCHI, HIDENARI
Publication of US20020002151A1 publication Critical patent/US20020002151A1/en
Application granted granted Critical
Publication of US6566350B2 publication Critical patent/US6566350B2/en
Assigned to SHOWA YAKUHIN KAKO CO., LTD. reassignment SHOWA YAKUHIN KAKO CO., LTD. CHANGE OF ADDRESS Assignors: SHOWA YAKUHIN KAKO CO., LTD.
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/42—Amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/65—Tetracyclines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S424/00—Drug, bio-affecting and body treating compositions
    • Y10S424/90—In vivo diagnostic or in vivo test agent which contains an additional ingredient to reduce the toxicity or side effects of the active ingredient

Definitions

  • the present invention relates to a pharmaceutical composition which comprises minocycline or a physiologically acceptable salt thereof as an active ingredient, and which is useful in the treatment or prevention of a periodontal disease such as periodontitis.
  • Periodontitis proximate periodontitis
  • Periodontitis is a chronic non-specific inflammation occurring not only in gingiva but also in other periodontia, which in most cases develops from periodontitis simplex.
  • gingiva gingiva
  • periodontia gingid tissue
  • periodontal pocket tooth loosening, alveolar bone absorption, and drainage from the pocket are observed, and most of them progress indolently.
  • certain gram negative bacilli within the periodontal sulcus are involved in periodontitis.
  • Bacteriodes gingivalis is involved in adult periodontitis
  • Actinobacillus actinomycetemcomitans is involved in juvenile periodontitis
  • Bacteriodes intermedius is involved in acute necrotizing ulcerative periodontitis (The Journal of the Japanese Society of Periodontology, Vol. 29 No. 2 pp463-471).
  • Minocycline is one type of tetracycline antibiotics which exhibits strong antibiotic action against the aforementioned periodontal pathogenic bacteria, and exhibits superior clinical efficacy against periodontitis (The Journal of the Japanese Society of Periodontology, Vol. 29 No. 2 pp472-483).
  • an ointment comprising minocycline hydrochloride (3.0%), hydroxymethylcellulose and glycerine to the periodontal pocket.
  • “Periocline dental ointment” is being used clinically as a periodontitis therapeutic agent.
  • minocycline is an unstable substance
  • techniques for providing a stable composition comprising minocycline as an active ingredient have been examined.
  • a non-aqueous composition for topical administration characterized in that minocycline or a physiologically acceptable salt thereof is formulated in a base of polyhydric alcohol which comprises a magnesium compound.
  • a base of polyhydric alcohol which comprises a magnesium compound.
  • compositions for treatment of periodontal diseases wherein minocycline or a physiologically acceptable salt thereof is formulated with a magnesium compound, an aqueous polymeric substance, a polyhydric alcohol, an ethyl methacrylate/ethyl methacrylate-trimethyl ammonium chloride copolymer, and a solubilizer.
  • a pharmaceutical composition for topical administration comprising minocycline or a physiologically acceptable salt thereof and an aluminium compound in a polyhydric alcohol base.
  • An object of the present invention is to provide a stable pharmaceutical composition for topical administration comprising minocycline as an active ingredient. Another object of the present invention is to provide a substance for stabilizing minocycline formulated in a pharmaceutical composition for topical administration.
  • the present inventors have found that, it was possible to achieve stabilization of minocycline in the oleaginous base, even without the use of stabilizers such as magnesium compounds or aluminium compounds, but with the use of an oleaginous base such as a gelated hydrocarbon in place of the conventionally used polyhydric alcohol.
  • the present invention was completed based on these findings.
  • a pharmaceutical composition for topical administration comprising minocycline or a physiologically acceptable salt thereof in an oleaginous base.
  • the oleaginous base is a gelated hydrocarbon. More preferably, the gelated hydrocarbon is plastibase.
  • the pharmaceutical composition according to the present invention preferably further comprises one or more adhesive agent selected from the group consisting of cellulose, cellulose derivatives, water-soluble high molecular compounds and water-soluble starch.
  • the pharmaceutical composition according to the present invention preferably further comprises a disintegrant.
  • a pharmaceutical composition comprising:
  • a pharmaceutical composition comprising:
  • the pharmaceutical composition of the present invention is preferably used in dental treatment and/or prevention, more preferably in treatment and/or prevention of periodontal diseases.
  • an oleaginous base which is used as a stabilizer of minocycline or a physiologically acceptable salt thereof.
  • the pharmaceutical composition of the present invention is characterized in that it comprises minocycline or a physiologically acceptable salt thereof in an oleaginous base.
  • the pharmaceutical composition of the present invention can be generally prepared as a pharmaceutical composition for topical administration to the oral cavity or periodontia, and preferably as a pharmaceutical composition for dental use.
  • the pharmaceutical composition according to the present invention is preferably provided such that it is suitable for topical administration to the oral cavity or periodontia, for example as a composition in a viscous liquid or paste form.
  • the pharmaceutical composition according to the present invention is useful in the treatment and/or prevention of oral cavity disease or disease in the dental area, for example, periodontal diseases such as periodontitis, periodontal disease, alveolar pyorrhea and the like.
  • the use of the pharmaceutical composition according to the present invention is not limited to the above embodiments and is able to be used as an external pharmaceutical composition on the skin or mucosa.
  • a physiologically acceptable salt of minocycline is not particularly limited.
  • mineral acid salts such as chloride, sulfate or acetate or organic acid salts such as methanesulfonate can be used.
  • Minocycline or a physiologically acceptable salt thereof may be a hydrate or solvate.
  • a solvent which forms the solvate is not particularly limited so long as it is physiologically acceptable, and for example, solvates of ethanol and the like may be used. It is preferred that hydrochloride is used as a salt of minocycline.
  • the content of minocycline or a physiologically acceptable salt thereof contained in the pharmaceutical composition of the present invention is generally about 0.01-15% by weight, preferably about 0.1-5% by weight (as the converted amount to free minocycline) relative to the weight of the composition.
  • the type of oleaginous base used in the pharmaceutical composition of the present invention is not particularly limited if it is one that is generally used in the pharmaceutical field.
  • gelated hydrocarbon Vaseline, squalane, isostearic acid, yellow beeswax, liquid paraffin, mid-chain fatty acid triglyceride, cottonseed oil and the like can be used alone or in combination of two or more of them.
  • a gelated hydrocarbon may be used.
  • Plastibase Billristol Myers Squibb
  • Poloid Maruishi Pharmaceutical
  • the content of the oleaginous base contained in the pharmaceutical composition of the present invention is generally 20-97% by weight, preferably 60-97% by weight, and more preferably 70-90% by weight relative to the weight of the composition.
  • one or more substances selected from the group consisting of cellulose, cellulose derivatives, and water-soluble high molecular compounds may be formulated as an adhesive agent.
  • cellulose crystalline cellulose can be used.
  • cellulose derivatives that can be used include sodium carboxymethylcellulose, cellulose acetate phtalate, hydroxyethylcellulose, hydroxypropylmethylcellulose and the like. Among these, hydroxypropylmethylcellulose is preferred.
  • water-soluble high molecular compounds include polyethylene glycol (Macrogol, etc.), polyvinyl alcohol, polyvinyl pyrolidon, Carragheenan, locust bean gum, arabia gum, xanthan gum, tragant gum, starch, etc.
  • the content of adhesive agent contained in the pharmaceutical composition of the present invention is generally about 1-60% by weight, preferably about 1-40% by weight, and more preferably about 5-20% by weight relative to the weight of the composition.
  • a disintegrant may be formulated.
  • the disintegrant that can be used are not particularly limited so long as it is one generally used in the pharmaceutical field.
  • examples of the disintegrant include sucrose fatty acid ester, glycerine fatty acid ester, sodium carboxymethylcellulose, lactose, sodium bicarbonate and the like.
  • Sucrose fatty acid ester can preferably be used.
  • sucrose fatty acid ester examples include sucrose stearate, sucrose palmitate, sucrose myristate, sucrose oleate, sucrose laureate, sucrose behenate, sucrose erucate, sucrose esters of mixed acid (oleic acid, palmitic and stearic acid) and the like.
  • the content of the disintegrant contained in the pharmaceutical composition of the present invention is generally about 1-20% by weight, preferably about 1-10% by weight relative to the weight of the composition.
  • magnesium compounds for example, the compounds described in Japanese Patent Publication No. 1-12728 and Japanese Patent Publication No. 2-34325
  • aluminium compounds for example, the compounds described in Japanese Patent Application Laid-Open No. 11-286448
  • the pharmaceutical composition of the present invention can be prepared according to conventional methods, and the method for preparation is not particularly limited.
  • the pharmaceutical composition of the present invention can easily be prepared by adding minocycline or a physiologically acceptable salt thereof, an oleaginous base such as gelated hydrocarbon, a disintegrant and an adhesive agent to a vessel in given amounts, and blending them as described in the Examples below.
  • additives for drug formulation available for those skilled in the art may be used appropriately.
  • a buffering agent, pH adjuster, surfactant, plasticizer, binder, dispersant, preservative and/or colorant, etc. may be formulated in the pharmaceutical composition of the present invention.
  • the content of these additives for drug manufacture can be appropriately selected by those skilled in the art such that it is suitable for pharmaceutical compositions for oral cavity use, dental use, or external use for applying to the skin or mucosa.
  • the pharmaceutical composition of the present invention can be prepared at a suitable elevated temperature where necessary, but in order to increase the stability of minocycline, it is preferred to prepare the pharmaceutical composition in a non-aqueous system.
  • the pharmaceutical composition of the present invention prepared as described above can be administered to a patient by directly applying it to the affected area (for example, to the periodontal disease area), and is preferably administered topically to the periodontal pocket.
  • the amount to be applied can be appropriately selected depending on the size of the affected area, extent of the disease, etc. For example, about 10-100 mg of the pharmaceutical composition of the present invention can be administered per tooth. Further, duration and number of administrations can be selected as appropriate.
  • the titer of post-storage minocycline was measured in accordance with the cylinder plate method described in Japanese Antibiotic Standard Commentary (1993).
  • the sample liquid was prepared as follows. A mass corresponding to approximately 10 mg (titer) was weighed precisely, and 10 ml of dimethyl formamide was added thereto to dissolve it. Then, 0.1M phosphate buffer (pH4.5) was added to bring the solution to exactly 100 ml, thereby preparing a solution having a concentration of about 0.1 mg (titer)/ml. An appropriate amount of this liquid was weighed out precisely and a sample solution of a prescribed concentration was prepared by precise dilution with 0.1M phosphate buffer (pH4.5).
  • Macrogol 1500 (30 g) and Macrogol 400 (20 g) were placed in a beaker and made uniform by heating/agitation with a hot stirrer. 44 g of this mixture, and 2 g (titer) of minocycline hydrochloride, 30 g of gelated hydrocarbon, 13.9 g of hydroxypropylmethylcellulose, 10 g of calcium chloride, and 0.1 g zinc sulfate were placed in a kneader and kneaded for 1 hour to produce 100 g of the pharmaceutical composition of the present invention.
  • a syringe was filled with the pharmaceutical composition prepared in Examples 4 and 5, and Comparative Example 1, tightly sealed, and stored for 15 hours at 50° C.
  • a change in characteristics was recognized in the composition of the Comparative Example, but no change was recognized in those of Examples 4 and 5.
  • the minocycline-containing pharmaceutical composition of the present invention is stable, and is particularly useful in the treatment and/or prevention of dental diseases such as periodontitis, periodontal disease, or alveolar pyorrhea.

Abstract

An object of the present invention is to provide a stable pharmaceutical composition for topical administration comprising minocycline as an active ingredient. According to the present invention, there is provided a pharmaceutical composition for topical administration comprising minocycline or a physiologically acceptable salt thereof in an oleaginous base.

Description

TECHNICAL FIELD OF THE INVENTION
The present invention relates to a pharmaceutical composition which comprises minocycline or a physiologically acceptable salt thereof as an active ingredient, and which is useful in the treatment or prevention of a periodontal disease such as periodontitis.
BACKGROUND ART
Periodontitis (proximate periodontitis) is a chronic non-specific inflammation occurring not only in gingiva but also in other periodontia, which in most cases develops from periodontitis simplex. In this disease, periodontal pocket, tooth loosening, alveolar bone absorption, and drainage from the pocket are observed, and most of them progress indolently. It is known that certain gram negative bacilli within the periodontal sulcus are involved in periodontitis. For example, Bacteriodes gingivalis is involved in adult periodontitis, Actinobacillus actinomycetemcomitans is involved in juvenile periodontitis, and Bacteriodes intermedius is involved in acute necrotizing ulcerative periodontitis (The Journal of the Japanese Society of Periodontology, Vol. 29 No. 2 pp463-471).
It is known that minocycline is effective in the treatment of periodontal diseases. Minocycline is one type of tetracycline antibiotics which exhibits strong antibiotic action against the aforementioned periodontal pathogenic bacteria, and exhibits superior clinical efficacy against periodontitis (The Journal of the Japanese Society of Periodontology, Vol. 29 No. 2 pp472-483). For example, there is proposed a method of directly applying an ointment comprising minocycline hydrochloride (3.0%), hydroxymethylcellulose and glycerine to the periodontal pocket. Further, “Periocline dental ointment” (sold by Sunstar Inc.) is being used clinically as a periodontitis therapeutic agent.
However, since minocycline is an unstable substance, techniques for providing a stable composition comprising minocycline as an active ingredient, have been examined. For example, in Japanese Patent Publication No. 1-12728, there is disclosed a non-aqueous composition for topical administration characterized in that minocycline or a physiologically acceptable salt thereof is formulated in a base of polyhydric alcohol which comprises a magnesium compound. Further, in Japanese Patent Publication No. 2-34325, there is disclosed a composition for treatment of periodontal diseases wherein minocycline or a physiologically acceptable salt thereof is formulated with a magnesium compound, an aqueous polymeric substance, a polyhydric alcohol, an ethyl methacrylate/ethyl methacrylate-trimethyl ammonium chloride copolymer, and a solubilizer. Furthermore, Japanese Patent Application Laid-Open No. 11-286448 discloses a pharmaceutical composition for topical administration comprising minocycline or a physiologically acceptable salt thereof and an aluminium compound in a polyhydric alcohol base.
SUMMARY OF THE INVENTION
An object of the present invention is to provide a stable pharmaceutical composition for topical administration comprising minocycline as an active ingredient. Another object of the present invention is to provide a substance for stabilizing minocycline formulated in a pharmaceutical composition for topical administration.
As a result of focused and deliberate efforts to achieve the above objects, the present inventors have found that, it was possible to achieve stabilization of minocycline in the oleaginous base, even without the use of stabilizers such as magnesium compounds or aluminium compounds, but with the use of an oleaginous base such as a gelated hydrocarbon in place of the conventionally used polyhydric alcohol. The present invention was completed based on these findings.
Thus, according to the present invention, there is provided a pharmaceutical composition for topical administration comprising minocycline or a physiologically acceptable salt thereof in an oleaginous base.
Preferably, the oleaginous base is a gelated hydrocarbon. More preferably, the gelated hydrocarbon is plastibase.
The pharmaceutical composition according to the present invention preferably further comprises one or more adhesive agent selected from the group consisting of cellulose, cellulose derivatives, water-soluble high molecular compounds and water-soluble starch.
The pharmaceutical composition according to the present invention preferably further comprises a disintegrant.
According to a preferred embodiment of the present invention, there is provided a pharmaceutical composition comprising:
(a) 0.01-15% by weight of minocycline or a physiologically acceptable salt thereof;
(b) 20-97% by weight of an oleaginous base;
(c) 1-60% by weight of an adhesive agent; and
(d) 1-20% by weight of a disintegrant
According to a more preferred embodiment of the present invention, there is provided a pharmaceutical composition comprising:
(a) 0.01-15% by weight of minocycline hydrochloride;
(b) 20-97% by weight of a gelated hydrocarbon;
(c) 1-60% by weight of hydroxypropylmethylcellulose, alpha-converted starch, carboxyvinyl polymer or methylcellulose; and,
(d) 1-20% by weight of a sucrose fatty acid ester.
The pharmaceutical composition of the present invention is preferably used in dental treatment and/or prevention, more preferably in treatment and/or prevention of periodontal diseases.
According to another aspect of the present invention, there is provided an oleaginous base which is used as a stabilizer of minocycline or a physiologically acceptable salt thereof.
DETAILED DESCRIPTION OF THE INVENTION
The pharmaceutical composition of the present invention is characterized in that it comprises minocycline or a physiologically acceptable salt thereof in an oleaginous base. The pharmaceutical composition of the present invention can be generally prepared as a pharmaceutical composition for topical administration to the oral cavity or periodontia, and preferably as a pharmaceutical composition for dental use. The pharmaceutical composition according to the present invention is preferably provided such that it is suitable for topical administration to the oral cavity or periodontia, for example as a composition in a viscous liquid or paste form. The pharmaceutical composition according to the present invention is useful in the treatment and/or prevention of oral cavity disease or disease in the dental area, for example, periodontal diseases such as periodontitis, periodontal disease, alveolar pyorrhea and the like. Moreover, the use of the pharmaceutical composition according to the present invention is not limited to the above embodiments and is able to be used as an external pharmaceutical composition on the skin or mucosa.
The type of a physiologically acceptable salt of minocycline is not particularly limited. For example, mineral acid salts such as chloride, sulfate or acetate or organic acid salts such as methanesulfonate can be used. Minocycline or a physiologically acceptable salt thereof may be a hydrate or solvate. A solvent which forms the solvate is not particularly limited so long as it is physiologically acceptable, and for example, solvates of ethanol and the like may be used. It is preferred that hydrochloride is used as a salt of minocycline. The content of minocycline or a physiologically acceptable salt thereof contained in the pharmaceutical composition of the present invention is generally about 0.01-15% by weight, preferably about 0.1-5% by weight (as the converted amount to free minocycline) relative to the weight of the composition.
The type of oleaginous base used in the pharmaceutical composition of the present invention is not particularly limited if it is one that is generally used in the pharmaceutical field. For example, gelated hydrocarbon, Vaseline, squalane, isostearic acid, yellow beeswax, liquid paraffin, mid-chain fatty acid triglyceride, cottonseed oil and the like can be used alone or in combination of two or more of them. Preferably, a gelated hydrocarbon may be used. Plastibase (Bristol Myers Squibb), Poloid (Maruishi Pharmaceutical) or the like can be used as the gelated hydrocarbon.
The content of the oleaginous base contained in the pharmaceutical composition of the present invention is generally 20-97% by weight, preferably 60-97% by weight, and more preferably 70-90% by weight relative to the weight of the composition.
In the pharmaceutical composition of the present invention, one or more substances selected from the group consisting of cellulose, cellulose derivatives, and water-soluble high molecular compounds may be formulated as an adhesive agent. As cellulose, crystalline cellulose can be used. Examples of cellulose derivatives that can be used include sodium carboxymethylcellulose, cellulose acetate phtalate, hydroxyethylcellulose, hydroxypropylmethylcellulose and the like. Among these, hydroxypropylmethylcellulose is preferred. Examples of water-soluble high molecular compounds include polyethylene glycol (Macrogol, etc.), polyvinyl alcohol, polyvinyl pyrolidon, Carragheenan, locust bean gum, arabia gum, xanthan gum, tragant gum, starch, etc.
The content of adhesive agent contained in the pharmaceutical composition of the present invention is generally about 1-60% by weight, preferably about 1-40% by weight, and more preferably about 5-20% by weight relative to the weight of the composition.
Further, in the pharmaceutical composition of the present invention, a disintegrant may be formulated. The disintegrant that can be used are not particularly limited so long as it is one generally used in the pharmaceutical field. Examples of the disintegrant include sucrose fatty acid ester, glycerine fatty acid ester, sodium carboxymethylcellulose, lactose, sodium bicarbonate and the like. Sucrose fatty acid ester can preferably be used. Examples of a sucrose fatty acid ester that can be used include sucrose stearate, sucrose palmitate, sucrose myristate, sucrose oleate, sucrose laureate, sucrose behenate, sucrose erucate, sucrose esters of mixed acid (oleic acid, palmitic and stearic acid) and the like.
The content of the disintegrant contained in the pharmaceutical composition of the present invention is generally about 1-20% by weight, preferably about 1-10% by weight relative to the weight of the composition.
Further, magnesium compounds (for example, the compounds described in Japanese Patent Publication No. 1-12728 and Japanese Patent Publication No. 2-34325) and/or aluminium compounds (for example, the compounds described in Japanese Patent Application Laid-Open No. 11-286448) may be formulated in the pharmaceutical composition of the present invention.
The pharmaceutical composition of the present invention can be prepared according to conventional methods, and the method for preparation is not particularly limited. For example, the pharmaceutical composition of the present invention can easily be prepared by adding minocycline or a physiologically acceptable salt thereof, an oleaginous base such as gelated hydrocarbon, a disintegrant and an adhesive agent to a vessel in given amounts, and blending them as described in the Examples below.
Further, when manufacturing the pharmaceutical composition of the present invention, additives for drug formulation available for those skilled in the art may be used appropriately. For example, a buffering agent, pH adjuster, surfactant, plasticizer, binder, dispersant, preservative and/or colorant, etc., may be formulated in the pharmaceutical composition of the present invention. The content of these additives for drug manufacture can be appropriately selected by those skilled in the art such that it is suitable for pharmaceutical compositions for oral cavity use, dental use, or external use for applying to the skin or mucosa. The pharmaceutical composition of the present invention can be prepared at a suitable elevated temperature where necessary, but in order to increase the stability of minocycline, it is preferred to prepare the pharmaceutical composition in a non-aqueous system.
The pharmaceutical composition of the present invention prepared as described above, can be administered to a patient by directly applying it to the affected area (for example, to the periodontal disease area), and is preferably administered topically to the periodontal pocket. The amount to be applied can be appropriately selected depending on the size of the affected area, extent of the disease, etc. For example, about 10-100 mg of the pharmaceutical composition of the present invention can be administered per tooth. Further, duration and number of administrations can be selected as appropriate.
The content of Japanese Patent Application No. 2000-150937, on which the present application claims a priority, is incorporated herein by reference.
The present invention will be further explained by examples below. However, these examples are not intended to limit the scope of the present invention.
EXAMPLES Example 1
2 g (titer) of minocycline hydrochloride, 73 g of gelated hydrocarbon (Plastibase; Bristol Myers Squibb), 20 g of hydroxypropylmethylcellulose and 5 g of sodium carboxymethylcellulose were placed in a kneader and kneaded for 1 hour to produce 100 g of the pharmaceutical composition of the present invention.
Example 2
2 g (titer) of minocycline hydrochloride, 68 g of gelated hydrocarbon (Plastibase; Bristol Myers Squibb), 10 g of sucrose fatty acid ester, and 20 g of hydroxypropylmethylcellulose were placed in a kneader and kneaded for 1 hour to produce 100 g of the pharmaceutical composition of the present invention.
Example 3
2 g of minocycline hydrochloride, 79 g of gelated hydrocarbon (Plastibase; Bristol Myers Squibb) and 5 g of sucrose fatty acid ester, and 14 g of hydroxypropylmethylcellulose were placed in a kneader and kneaded for 1 hour to produce the pharmaceutical composition of the present invention.
Test Example 1
The pharmaceutical compositions of the present invention prepared in Examples 1 to 3, were stored for 6 months under the condition of 30° C. and 70% relative humidity. The titer of post-storage minocycline was measured in accordance with the cylinder plate method described in Japanese Antibiotic Standard Commentary (1993). The sample liquid was prepared as follows. A mass corresponding to approximately 10 mg (titer) was weighed precisely, and 10 ml of dimethyl formamide was added thereto to dissolve it. Then, 0.1M phosphate buffer (pH4.5) was added to bring the solution to exactly 100 ml, thereby preparing a solution having a concentration of about 0.1 mg (titer)/ml. An appropriate amount of this liquid was weighed out precisely and a sample solution of a prescribed concentration was prepared by precise dilution with 0.1M phosphate buffer (pH4.5).
As a result of this measurement, no significant reduction in titer of minocycline hidrochloride could be recognized in respect of any of the pharmaceutical compositions of Examples 1 to 3
Example 4
Macrogol 1500 (30 g) and Macrogol 400 (20 g) were placed in a beaker and made uniform by heating/agitation with a hot stirrer. 44 g of this mixture, and 2 g (titer) of minocycline hydrochloride, 30 g of gelated hydrocarbon, 13.9 g of hydroxypropylmethylcellulose, 10 g of calcium chloride, and 0.1 g zinc sulfate were placed in a kneader and kneaded for 1 hour to produce 100 g of the pharmaceutical composition of the present invention.
Example 5
86 g of white Vaseline, 3 g of cholesterol, 3 g of stearyl alcohol, 8 g of white beeswax were placed in a beaker and made uniform by heating/agitation with a hot stirrer. 93 g of this mixture, 2 g (titer) of minocycline hydrochloride, 5 g carboxyvinyl polymer were placed in a kneader and kneaded for 1 hour to produce 100 g of the pharmaceutical composition of the present invention.
Comparative Example 1
2 g (titer) of minocycline hydrochloride, 95 g of concentrated glycerin, and 3 g of sodium carboxymethylcellulose were placed in a kneader and kneaded for 1 hour to produce 100 g of the pharmaceutical composition of the present invention.
Test Example 2
A syringe was filled with the pharmaceutical composition prepared in Examples 4 and 5, and Comparative Example 1, tightly sealed, and stored for 15 hours at 50° C. As a result of comparing each of the post-storage compositions of Examples 4 and 5, and Comparative example 1, a change in characteristics was recognized in the composition of the Comparative Example, but no change was recognized in those of Examples 4 and 5.
Industrially Applicable Field
The minocycline-containing pharmaceutical composition of the present invention is stable, and is particularly useful in the treatment and/or prevention of dental diseases such as periodontitis, periodontal disease, or alveolar pyorrhea.

Claims (14)

What is claimed is:
1. A pharmaceutical composition comprising:
0.01-15% by weight of minocycline or a physiologically acceptable salt thereof;
20-97% % by weight of an oleaginous base;
1-60% by weight of an adhesive agent; and,
1-20% by weight of a sucrose fatty acid ester.
2. The pharmaceutical composition according to claim 1 wherein the oleaginous base is a gelated hydrocarbon.
3. The pharmaceutical composition according to claim 1 further comprising at least one adhesive agent selected from the group consisting of cellulose, cellulose derivatives, water-soluble high molecular compounds, and water-soluble starch.
4. The pharmaceutical composition according to claim 1, which comprises:
0.01-15% by weight of minocycline hydrochloride;
20-97% by weight of a gelated hydrocarbon;
1-60% by weight of a hydroxypropylmethylcellulose, alpha-converted starch, carboxyvinyl polymer or methylcellulose; and
1-20% by weight of a sucrose fatty acid ester.
5. A method for at least one of treatment and prevention of dental diseases comprising topically administering to a patient a pharmaceutical composition comprising minocycline or a physiologically acceptable salt thereof, an oleaginous base and a sucrose fatty acid ester.
6. The method according to claim 5 wherein the at least one of treatment and prevention of dental diseases comprises at least one of treatment and prevention of a periodontal disease.
7. A method of stabilizing a minocycline or a physiologically acceptable salt thereof comprising combining the minocycline or a physiologically acceptable salt thereof with an oleaginous base and a sucrose fatty acid ester.
8. The method according to claim 5 wherein the oleaginous base is a gelated hydrocarbon.
9. The method according to claim 5, wherein the pharmaceutical composition comprises:
0.01-15% by weight of minocycline or a physiologically acceptable salt thereof;
20-97% by weight of an oleaginous base;
1-60% by weight of an adhesive agent; and,
1-20% by weight of a sucrose fatty acid ester.
10. The method according to claim 9, which comprises:
0.01-15% by weight of minocycline hydrochloride;
20-97% by weight of a gelated hydrocarbon;
1-60% by weight of a hydroxypropylmethylcellulose, alpha-converted starch, carboxyvinyl polymer or methylcellulose; and,
1-20% by weight of a sucrose fatty acid ester.
11. The method according to claim 6 wherein the oleaginous base is a gelated hydrocarbon.
12. The method according to claim 6, wherein the pharmaceutical composition comprises:
0.01-15% by weight of minocycline or a physiologically acceptable salt thereof;
20-97% by weight of an oleaginous base;
1-60% by weight of an adhesive agent; and,
1-20% by weight of a sucrose fatty acid ester.
13. The method according to claim 12, wherein comprises:
0.01-15% by weight of minocycline hydrochloride;
20-97% by weight of a gelated hydrocarbon;
1-60% by weight of a hydroxypropylmethylcellulose, alpha-converted starch, carboxyvinyl polymer or methylcellulose; and,
1-20% by weight of a sucrose fatty acid ester.
14. The method according to claim 7 wherein the oleaginous base is a gelated hydrocarbon.
US09/860,503 2000-05-23 2001-05-21 Minocycline-containing compositions Expired - Lifetime US6566350B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP2000150937A JP4653282B2 (en) 2000-05-23 2000-05-23 Minocycline-containing composition
JP150937/2000 2000-05-23
JP2000-150937 2000-05-23

Publications (2)

Publication Number Publication Date
US20020002151A1 US20020002151A1 (en) 2002-01-03
US6566350B2 true US6566350B2 (en) 2003-05-20

Family

ID=18656568

Family Applications (1)

Application Number Title Priority Date Filing Date
US09/860,503 Expired - Lifetime US6566350B2 (en) 2000-05-23 2001-05-21 Minocycline-containing compositions

Country Status (4)

Country Link
US (1) US6566350B2 (en)
JP (1) JP4653282B2 (en)
KR (1) KR100884575B1 (en)
TW (1) TWI285551B (en)

Cited By (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050237882A1 (en) * 2004-04-23 2005-10-27 Sanyo Electric Co., Ltd. Tracking balance adjustment device
US20080188446A1 (en) * 2007-02-02 2008-08-07 Warner Chilcott Company Inc. Tetracycline compositions for topical administration
US20080188445A1 (en) * 2007-02-02 2008-08-07 Warner Chilcott Company Inc. Tetracycline compositions for topical administration
US20100068238A1 (en) * 2005-07-15 2010-03-18 Nandkishore Managoli Implantable Medical Devices Comprising a Flavonoid or Derivative Thereof for Prevention of Restenosis
US8114385B2 (en) 2003-08-04 2012-02-14 Foamix Ltd. Oleaginous pharmaceutical and cosmetic foam
US8119109B2 (en) 2002-10-25 2012-02-21 Foamix Ltd. Foamable compositions, kits and methods for hyperhidrosis
US8119150B2 (en) 2002-10-25 2012-02-21 Foamix Ltd. Non-flammable insecticide composition and uses thereof
US8119106B2 (en) 2003-04-28 2012-02-21 Foamix Ltd Foamable iodine compositions
US8343945B2 (en) 2007-12-07 2013-01-01 Foamix Ltd. Carriers, formulations, methods for formulating unstable active agents for external application and uses thereof
US8362091B2 (en) 2003-08-04 2013-01-29 Foamix Ltd. Foamable vehicle and pharmaceutical compositions thereof
US8435498B2 (en) 2002-10-25 2013-05-07 Foamix Ltd. Penetrating pharmaceutical foam
US8486376B2 (en) 2002-10-25 2013-07-16 Foamix Ltd. Moisturizing foam containing lanolin
US8486374B2 (en) 2003-08-04 2013-07-16 Foamix Ltd. Hydrophilic, non-aqueous pharmaceutical carriers and compositions and uses
US8512718B2 (en) 2000-07-03 2013-08-20 Foamix Ltd. Pharmaceutical composition for topical application
US8518376B2 (en) 2007-12-07 2013-08-27 Foamix Ltd. Oil-based foamable carriers and formulations
US8618081B2 (en) 2009-10-02 2013-12-31 Foamix Ltd. Compositions, gels and foams with rheology modulators and uses thereof
US8636982B2 (en) 2007-08-07 2014-01-28 Foamix Ltd. Wax foamable vehicle and pharmaceutical compositions thereof
US8709385B2 (en) 2008-01-14 2014-04-29 Foamix Ltd. Poloxamer foamable pharmaceutical compositions with active agents and/or therapeutic cells and uses
US8722021B2 (en) 2002-10-25 2014-05-13 Foamix Ltd. Foamable carriers
US8760906B2 (en) 2009-11-24 2014-06-24 Micron Technology, Inc. Techniques for reducing disturbance in a semiconductor memory device
US8795693B2 (en) 2003-08-04 2014-08-05 Foamix Ltd. Compositions with modulating agents
US8795635B2 (en) 2006-11-14 2014-08-05 Foamix Ltd. Substantially non-aqueous foamable petrolatum based pharmaceutical and cosmetic compositions and their uses
US20140221320A1 (en) * 2011-07-08 2014-08-07 The Research Foundation For The State University Of New York Topical minocycline ointment for suppression of allergic skin responses
WO2014152790A1 (en) * 2013-03-14 2014-09-25 Drexel University Chelated drug delivery systems
US8900554B2 (en) 2002-10-25 2014-12-02 Foamix Pharmaceuticals Ltd. Foamable composition and uses thereof
US9072667B2 (en) 2009-07-29 2015-07-07 Foamix Pharmaceuticals Ltd. Non surface active agent non polymeric agent hydro-alcoholic foamable compositions, breakable foams and their uses
US9167813B2 (en) 2009-07-29 2015-10-27 Foamix Pharmaceuticals Ltd. Non surfactant hydro-alcoholic foamable compositions, breakable foams and their uses
US9211259B2 (en) 2002-11-29 2015-12-15 Foamix Pharmaceuticals Ltd. Antibiotic kit and composition and uses thereof
US9265725B2 (en) 2002-10-25 2016-02-23 Foamix Pharmaceuticals Ltd. Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof
US9320705B2 (en) 2002-10-25 2016-04-26 Foamix Pharmaceuticals Ltd. Sensation modifying topical composition foam
US9439857B2 (en) 2007-11-30 2016-09-13 Foamix Pharmaceuticals Ltd. Foam containing benzoyl peroxide
US9539208B2 (en) 2002-10-25 2017-01-10 Foamix Pharmaceuticals Ltd. Foam prepared from nanoemulsions and uses
US9622947B2 (en) 2002-10-25 2017-04-18 Foamix Pharmaceuticals Ltd. Foamable composition combining a polar solvent and a hydrophobic carrier
US9668972B2 (en) 2002-10-25 2017-06-06 Foamix Pharmaceuticals Ltd. Nonsteroidal immunomodulating kit and composition and uses thereof
US9849142B2 (en) 2009-10-02 2017-12-26 Foamix Pharmaceuticals Ltd. Methods for accelerated return of skin integrity and for the treatment of impetigo
US9884017B2 (en) 2009-04-28 2018-02-06 Foamix Pharmaceuticals Ltd. Foamable vehicles and pharmaceutical compositions comprising aprotic polar solvents and uses thereof
US9918998B2 (en) 2015-03-23 2018-03-20 BioPharmX, Inc. Pharmaceutical tetracycline composition for dermatological use
US10398641B2 (en) 2016-09-08 2019-09-03 Foamix Pharmaceuticals Ltd. Compositions and methods for treating rosacea and acne

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050205086A1 (en) * 2002-10-25 2005-09-22 Foamix Ltd. Retinoid immunomodulating kit and composition and uses thereof
US20060193789A1 (en) * 2002-10-25 2006-08-31 Foamix Ltd. Film forming foamable composition
US20050186142A1 (en) * 2002-10-25 2005-08-25 Foamix Ltd. Kit and composition of imidazole with enhanced bioavailability
US20050271596A1 (en) * 2002-10-25 2005-12-08 Foamix Ltd. Vasoactive kit and composition and uses thereof
US20070292359A1 (en) * 2002-10-25 2007-12-20 Foamix Ltd. Polypropylene glycol foamable vehicle and pharmaceutical compositions thereof
US20070292355A1 (en) * 2002-10-25 2007-12-20 Foamix Ltd. Anti-infection augmentation foamable compositions and kit and uses thereof
US20080317679A1 (en) * 2002-10-25 2008-12-25 Foamix Ltd. Foamable compositions and kits comprising one or more of a channel agent, a cholinergic agent, a nitric oxide donor, and related agents and their uses
US20080206161A1 (en) * 2002-10-25 2008-08-28 Dov Tamarkin Quiescent foamable compositions, steroids, kits and uses thereof
US20080069779A1 (en) * 2003-08-04 2008-03-20 Foamix Ltd. Foamable vehicle and vitamin and flavonoid pharmaceutical compositions thereof
AU2004261063A1 (en) * 2003-08-04 2005-02-10 Foamix Ltd. Foam carrier containing amphiphilic copolymeric gelling agent
US20050075407A1 (en) * 2003-08-25 2005-04-07 Foamix Ltd. Foam incorporating eutetic mixture
US20080166303A1 (en) * 2006-09-08 2008-07-10 Dov Tamarkin Colored or colorable foamable composition and foam
EP2073794A2 (en) * 2006-11-14 2009-07-01 Foamix Ltd. Stable non-alcoholic foamable pharmaceutical emulsion compositions with an unctuous emollient and their uses
US20080292560A1 (en) * 2007-01-12 2008-11-27 Dov Tamarkin Silicone in glycol pharmaceutical and cosmetic compositions with accommodating agent
US20090130029A1 (en) * 2007-11-21 2009-05-21 Foamix Ltd. Glycerol ethers vehicle and pharmaceutical compositions thereof
KR101406106B1 (en) * 2011-12-19 2014-06-13 동국제약 주식회사 Locally applied composition of sustained-release for treating periodontal diseases
CN102670486A (en) * 2012-05-04 2012-09-19 安徽医科大学 Method for preparing injectable minocycline ointment
PT106679B (en) * 2012-11-27 2015-03-25 Hovione Farmaciencia Sa TOPICAL FORMULATIONS OF TETRACYCLINES, THEIR PREPARATION AND USES
JP6474624B2 (en) * 2015-01-28 2019-02-27 昭和薬品化工株式会社 Caries remover
WO2018124324A1 (en) * 2016-12-27 2018-07-05 주식회사 쿠보텍 Ointment composition for improving periodontitis

Citations (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2627938A (en) * 1948-08-10 1953-02-10 Res Prod Corp Method of making high viscosity products having petroleum oil base and product of such method
US2628187A (en) * 1950-05-06 1953-02-10 Res Prod Corp Medicinal mineral oil vehicle thickened with polyethylene
US4164564A (en) * 1976-12-23 1979-08-14 E. R. Squibb & Sons, Inc. Ointment and cream bases capable of withstanding elevated temperatures
US4254105A (en) * 1975-10-11 1981-03-03 The Lion Dentifrice Co., Ltd. Multiple emulsion having a form of water/oil/water phase and process for preparation thereof, and multiple emulsion type cosmetics
US4379755A (en) * 1978-08-10 1983-04-12 Nihon Surfactant Industry Co., Ltd. Gelatinizing agent composition, and gel and aqueous emulsion prepared therefrom
US4427670A (en) * 1980-03-27 1984-01-24 Mitsubishi Chemical Industries Limited Skin preparation
US4536519A (en) * 1981-06-15 1985-08-20 Kao Soap Co., Ltd. Emulsifying agent and emulsified cosmetics
JPS6412728A (en) 1987-07-07 1989-01-17 Fujitsu Ltd Echo canceller
JPS6483019A (en) * 1987-09-25 1989-03-28 Sunstar Inc Composition used in oral cavity for orthodontic therapy of tooth
US4822601A (en) * 1987-03-13 1989-04-18 R.I.T.A. Corporation Cosmetic base composition with therapeutic properties
US4867970A (en) * 1987-05-21 1989-09-19 E. R. Squibb & Sons, Inc. Moistureless oral drug delivery formulation and method for preparing same
USRE33093E (en) * 1986-06-16 1989-10-17 Johnson & Johnson Consumer Products, Inc. Bioadhesive extruded film for intra-oral drug delivery and process
US4882359A (en) * 1986-04-08 1989-11-21 Hisamitsu Pharmaceutical Co., Ltd. Azacycloalkane derivatives, absorption promoters containing the derivatives as the effective ingredient and external preparations containing the absorption promoters
JPH0234325A (en) 1988-07-26 1990-02-05 Nanjiyou Sobi Kogyo Kk Manufacture of laminate
US4946832A (en) * 1987-03-13 1990-08-07 R.I.T.A. Corporation Cosmetic base composition with therapeutic properties
US4965262A (en) * 1987-02-26 1990-10-23 Rohto Pharmaceutical Co., Ltd. Method for treating or preventing locally periodontal disease
US4981693A (en) * 1986-03-25 1991-01-01 Rohto Pharmaceutical Co., Ltd. Pharmaceutical composition for periodontal diseases
US4981875A (en) * 1987-08-12 1991-01-01 Bayer Aktiengesellschaft Medicaments for the region of the oral cavity
US4983385A (en) * 1985-11-22 1991-01-08 Sunstar Kabushiki Kaisha Ointment base
JPH0413616A (en) * 1990-04-27 1992-01-17 Toyama Chem Co Ltd Sustained release ointment for oral cavity
US5112816A (en) * 1989-06-21 1992-05-12 Ss Pharmaceutical Co., Ltd. Corticorsteroid-containing ointments
US5122519A (en) * 1989-06-27 1992-06-16 American Cyanamid Company Stable, cosmetically acceptable topical gel formulation and method of treatment for acne
US5322689A (en) * 1992-03-10 1994-06-21 The Procter & Gamble Company Topical aromatic releasing compositions
WO1994020144A1 (en) * 1993-03-10 1994-09-15 Nippon Kayaku Kabushiki Kaisha Paste and paste preparation
JPH0789847A (en) * 1991-10-24 1995-04-04 Toyama Chem Co Ltd Sustained release ointment for oral cavity
US5580549A (en) * 1992-05-15 1996-12-03 Shiseido Co., Ltd. External preparation for skin
US5614178A (en) * 1992-07-28 1997-03-25 The Procter & Gamble Company Compositions for topical delivery of drugs comprising a mixture of high and low HLB surfactants and alkoxylated ether
US5631248A (en) * 1992-04-10 1997-05-20 Smithkline Beecham Plc Supersaturated topical compositions
US5641493A (en) * 1993-02-09 1997-06-24 The Procter & Gamble Company Cosmetic compositions
US5674509A (en) * 1993-02-09 1997-10-07 The Procter & Gamble Company Cosmetic compositions
JPH10245329A (en) * 1997-03-05 1998-09-14 Shiseido Co Ltd Composition for oral cavity
US5858408A (en) * 1994-07-20 1999-01-12 Toyama Chemical Co., Ltd. Sustained-release oral ointment
US5879689A (en) * 1995-08-09 1999-03-09 The Procter & Gamble Company Cosmetic compositions
JPH11286448A (en) 1998-04-01 1999-10-19 Showa Yakuhin Kako Kk Composition containing minocycline
US6096325A (en) * 1993-02-09 2000-08-01 The Procter & Gamble Company Oil-in-water skin composition comprising silicone gum and fatty acid ester capable of forming liquid crystals
USH2043H1 (en) * 1997-05-23 2002-08-06 The Procter & Gamble Company Skin care compositions
US6444647B1 (en) * 1999-04-19 2002-09-03 The Procter & Gamble Company Skin care compositions containing combination of skin care actives
US6492326B1 (en) * 1999-04-19 2002-12-10 The Procter & Gamble Company Skin care compositions containing combination of skin care actives

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0234325B2 (en) * 1985-11-22 1990-08-02 Sansutaa Kk SHISHUSHITSUKANCHIRYOYOSOSEIBUTSU
JPS61130228A (en) * 1984-11-29 1986-06-18 Sunstar Inc Composition stably blended with minocycline
US4701320A (en) * 1984-11-29 1987-10-20 Lederle (Japan), Ltd. Composition stably containing minocycline for treating periodontal diseases
US4935228A (en) * 1987-12-28 1990-06-19 L'oreal S.A. Lip gloss
JPH02200624A (en) * 1989-01-30 1990-08-08 Nippon Kayaku Co Ltd Dental dressing agent
JPH06211650A (en) * 1993-01-12 1994-08-02 Terumo Corp Ointment adhesive to oral cavity
JPH0733643A (en) * 1993-07-16 1995-02-03 G C:Kk Base for periodontal administration and pharmaceutical preparation therefor
JPH0769851A (en) * 1993-09-03 1995-03-14 Lion Corp Composition for oral cavity
JPH08268854A (en) * 1995-03-31 1996-10-15 Sunstar Inc Composition for oral cavity
WO1999036098A1 (en) * 1998-01-13 1999-07-22 Suntory Limited Antibacterial composition for topical administration containing antibiotics

Patent Citations (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2627938A (en) * 1948-08-10 1953-02-10 Res Prod Corp Method of making high viscosity products having petroleum oil base and product of such method
US2628187A (en) * 1950-05-06 1953-02-10 Res Prod Corp Medicinal mineral oil vehicle thickened with polyethylene
US4254105A (en) * 1975-10-11 1981-03-03 The Lion Dentifrice Co., Ltd. Multiple emulsion having a form of water/oil/water phase and process for preparation thereof, and multiple emulsion type cosmetics
US4164564A (en) * 1976-12-23 1979-08-14 E. R. Squibb & Sons, Inc. Ointment and cream bases capable of withstanding elevated temperatures
US4379755A (en) * 1978-08-10 1983-04-12 Nihon Surfactant Industry Co., Ltd. Gelatinizing agent composition, and gel and aqueous emulsion prepared therefrom
US4427670A (en) * 1980-03-27 1984-01-24 Mitsubishi Chemical Industries Limited Skin preparation
US4536519A (en) * 1981-06-15 1985-08-20 Kao Soap Co., Ltd. Emulsifying agent and emulsified cosmetics
US4983385A (en) * 1985-11-22 1991-01-08 Sunstar Kabushiki Kaisha Ointment base
US4981693A (en) * 1986-03-25 1991-01-01 Rohto Pharmaceutical Co., Ltd. Pharmaceutical composition for periodontal diseases
US4882359A (en) * 1986-04-08 1989-11-21 Hisamitsu Pharmaceutical Co., Ltd. Azacycloalkane derivatives, absorption promoters containing the derivatives as the effective ingredient and external preparations containing the absorption promoters
USRE33093E (en) * 1986-06-16 1989-10-17 Johnson & Johnson Consumer Products, Inc. Bioadhesive extruded film for intra-oral drug delivery and process
US4965262A (en) * 1987-02-26 1990-10-23 Rohto Pharmaceutical Co., Ltd. Method for treating or preventing locally periodontal disease
US4822601A (en) * 1987-03-13 1989-04-18 R.I.T.A. Corporation Cosmetic base composition with therapeutic properties
US4946832A (en) * 1987-03-13 1990-08-07 R.I.T.A. Corporation Cosmetic base composition with therapeutic properties
US4867970A (en) * 1987-05-21 1989-09-19 E. R. Squibb & Sons, Inc. Moistureless oral drug delivery formulation and method for preparing same
JPS6412728A (en) 1987-07-07 1989-01-17 Fujitsu Ltd Echo canceller
US4981875A (en) * 1987-08-12 1991-01-01 Bayer Aktiengesellschaft Medicaments for the region of the oral cavity
JPS6483019A (en) * 1987-09-25 1989-03-28 Sunstar Inc Composition used in oral cavity for orthodontic therapy of tooth
JPH0234325A (en) 1988-07-26 1990-02-05 Nanjiyou Sobi Kogyo Kk Manufacture of laminate
US5112816A (en) * 1989-06-21 1992-05-12 Ss Pharmaceutical Co., Ltd. Corticorsteroid-containing ointments
US5122519A (en) * 1989-06-27 1992-06-16 American Cyanamid Company Stable, cosmetically acceptable topical gel formulation and method of treatment for acne
JPH0413616A (en) * 1990-04-27 1992-01-17 Toyama Chem Co Ltd Sustained release ointment for oral cavity
JPH0789847A (en) * 1991-10-24 1995-04-04 Toyama Chem Co Ltd Sustained release ointment for oral cavity
US5322689A (en) * 1992-03-10 1994-06-21 The Procter & Gamble Company Topical aromatic releasing compositions
US5631248A (en) * 1992-04-10 1997-05-20 Smithkline Beecham Plc Supersaturated topical compositions
US5580549A (en) * 1992-05-15 1996-12-03 Shiseido Co., Ltd. External preparation for skin
US5614178A (en) * 1992-07-28 1997-03-25 The Procter & Gamble Company Compositions for topical delivery of drugs comprising a mixture of high and low HLB surfactants and alkoxylated ether
US5641493A (en) * 1993-02-09 1997-06-24 The Procter & Gamble Company Cosmetic compositions
US5674509A (en) * 1993-02-09 1997-10-07 The Procter & Gamble Company Cosmetic compositions
US6096325A (en) * 1993-02-09 2000-08-01 The Procter & Gamble Company Oil-in-water skin composition comprising silicone gum and fatty acid ester capable of forming liquid crystals
WO1994020144A1 (en) * 1993-03-10 1994-09-15 Nippon Kayaku Kabushiki Kaisha Paste and paste preparation
US5858408A (en) * 1994-07-20 1999-01-12 Toyama Chemical Co., Ltd. Sustained-release oral ointment
US5879689A (en) * 1995-08-09 1999-03-09 The Procter & Gamble Company Cosmetic compositions
JPH10245329A (en) * 1997-03-05 1998-09-14 Shiseido Co Ltd Composition for oral cavity
USH2043H1 (en) * 1997-05-23 2002-08-06 The Procter & Gamble Company Skin care compositions
JPH11286448A (en) 1998-04-01 1999-10-19 Showa Yakuhin Kako Kk Composition containing minocycline
US6444647B1 (en) * 1999-04-19 2002-09-03 The Procter & Gamble Company Skin care compositions containing combination of skin care actives
US6492326B1 (en) * 1999-04-19 2002-12-10 The Procter & Gamble Company Skin care compositions containing combination of skin care actives

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
Abstract of Registered Trademark 617115 "Plastibase" Medicinal (Squibb) Ointment Base, Dec. 1955.* *
Abstract of Sotani et al JP 07089847 (Apr. 1995) U.S. 5858408 Nov. 1999.* *
Abstract of Tanaka et al Yakuzagaku 57(1): 8-15, 1997.* *
English Language Abstract of JP 1-12728.
English Language Abstract of JP 11-286448.
English Language Abstract of JP 2-34325.
The Journal of the Japanese Society of Periodontology, vol. 29, No. 2, pp. 463-471, 472-843, 1987.
The Journal of the Japanese Society of Periodontology, vol. 29, No. 2, pp. 472-843, 1987 (accompanied by an English language abstract).

Cited By (93)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8512718B2 (en) 2000-07-03 2013-08-20 Foamix Ltd. Pharmaceutical composition for topical application
US9668972B2 (en) 2002-10-25 2017-06-06 Foamix Pharmaceuticals Ltd. Nonsteroidal immunomodulating kit and composition and uses thereof
US9265725B2 (en) 2002-10-25 2016-02-23 Foamix Pharmaceuticals Ltd. Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof
US10322085B2 (en) 2002-10-25 2019-06-18 Foamix Pharmaceuticals Ltd. Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof
US9622947B2 (en) 2002-10-25 2017-04-18 Foamix Pharmaceuticals Ltd. Foamable composition combining a polar solvent and a hydrophobic carrier
US8119109B2 (en) 2002-10-25 2012-02-21 Foamix Ltd. Foamable compositions, kits and methods for hyperhidrosis
US8119150B2 (en) 2002-10-25 2012-02-21 Foamix Ltd. Non-flammable insecticide composition and uses thereof
US9492412B2 (en) 2002-10-25 2016-11-15 Foamix Pharmaceuticals Ltd. Penetrating pharmaceutical foam
US8741265B2 (en) 2002-10-25 2014-06-03 Foamix Ltd. Penetrating pharmaceutical foam
US8900554B2 (en) 2002-10-25 2014-12-02 Foamix Pharmaceuticals Ltd. Foamable composition and uses thereof
US8435498B2 (en) 2002-10-25 2013-05-07 Foamix Ltd. Penetrating pharmaceutical foam
US8486376B2 (en) 2002-10-25 2013-07-16 Foamix Ltd. Moisturizing foam containing lanolin
US9713643B2 (en) 2002-10-25 2017-07-25 Foamix Pharmaceuticals Ltd. Foamable carriers
US8722021B2 (en) 2002-10-25 2014-05-13 Foamix Ltd. Foamable carriers
US8840869B2 (en) 2002-10-25 2014-09-23 Foamix Ltd. Body cavity foams
US10117812B2 (en) 2002-10-25 2018-11-06 Foamix Pharmaceuticals Ltd. Foamable composition combining a polar solvent and a hydrophobic carrier
US11033491B2 (en) 2002-10-25 2021-06-15 Vyne Therapeutics Inc. Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof
US10821077B2 (en) 2002-10-25 2020-11-03 Foamix Pharmaceuticals Ltd. Dicarboxylic acid foamable vehicle and pharmaceutical compositions thereof
US9320705B2 (en) 2002-10-25 2016-04-26 Foamix Pharmaceuticals Ltd. Sensation modifying topical composition foam
US9539208B2 (en) 2002-10-25 2017-01-10 Foamix Pharmaceuticals Ltd. Foam prepared from nanoemulsions and uses
US9211259B2 (en) 2002-11-29 2015-12-15 Foamix Pharmaceuticals Ltd. Antibiotic kit and composition and uses thereof
US8119106B2 (en) 2003-04-28 2012-02-21 Foamix Ltd Foamable iodine compositions
US8486375B2 (en) 2003-04-28 2013-07-16 Foamix Ltd. Foamable compositions
US8114385B2 (en) 2003-08-04 2012-02-14 Foamix Ltd. Oleaginous pharmaceutical and cosmetic foam
US9050253B2 (en) 2003-08-04 2015-06-09 Foamix Pharmaceuticals Ltd. Oleaginous pharmaceutical and cosmetic foam
US8486374B2 (en) 2003-08-04 2013-07-16 Foamix Ltd. Hydrophilic, non-aqueous pharmaceutical carriers and compositions and uses
US8518378B2 (en) 2003-08-04 2013-08-27 Foamix Ltd. Oleaginous pharmaceutical and cosmetic foam
US9101662B2 (en) 2003-08-04 2015-08-11 Foamix Pharmaceuticals Ltd. Compositions with modulating agents
US8362091B2 (en) 2003-08-04 2013-01-29 Foamix Ltd. Foamable vehicle and pharmaceutical compositions thereof
US8795693B2 (en) 2003-08-04 2014-08-05 Foamix Ltd. Compositions with modulating agents
US8703105B2 (en) 2003-08-04 2014-04-22 Foamix Ltd. Oleaginous pharmaceutical and cosmetic foam
US9636405B2 (en) 2003-08-04 2017-05-02 Foamix Pharmaceuticals Ltd. Foamable vehicle and pharmaceutical compositions thereof
US20050237882A1 (en) * 2004-04-23 2005-10-27 Sanyo Electric Co., Ltd. Tracking balance adjustment device
US20100068238A1 (en) * 2005-07-15 2010-03-18 Nandkishore Managoli Implantable Medical Devices Comprising a Flavonoid or Derivative Thereof for Prevention of Restenosis
US9682021B2 (en) 2006-11-14 2017-06-20 Foamix Pharmaceuticals Ltd. Substantially non-aqueous foamable petrolatum based pharmaceutical and cosmetic compositions and their uses
US8795635B2 (en) 2006-11-14 2014-08-05 Foamix Ltd. Substantially non-aqueous foamable petrolatum based pharmaceutical and cosmetic compositions and their uses
US20080188445A1 (en) * 2007-02-02 2008-08-07 Warner Chilcott Company Inc. Tetracycline compositions for topical administration
US20080188446A1 (en) * 2007-02-02 2008-08-07 Warner Chilcott Company Inc. Tetracycline compositions for topical administration
US11103454B2 (en) 2007-08-07 2021-08-31 Vyne Therapeutics Inc. Wax foamable vehicle and pharmaceutical compositions thereof
US9662298B2 (en) 2007-08-07 2017-05-30 Foamix Pharmaceuticals Ltd. Wax foamable vehicle and pharmaceutical compositions thereof
US10369102B2 (en) 2007-08-07 2019-08-06 Foamix Pharmaceuticals Ltd. Wax foamable vehicle and pharmaceutical compositions thereof
US8636982B2 (en) 2007-08-07 2014-01-28 Foamix Ltd. Wax foamable vehicle and pharmaceutical compositions thereof
US9439857B2 (en) 2007-11-30 2016-09-13 Foamix Pharmaceuticals Ltd. Foam containing benzoyl peroxide
US9549898B2 (en) 2007-12-07 2017-01-24 Foamix Pharmaceuticals Ltd. Oil and liquid silicone foamable carriers and formulations
US8518376B2 (en) 2007-12-07 2013-08-27 Foamix Ltd. Oil-based foamable carriers and formulations
US9161916B2 (en) 2007-12-07 2015-10-20 Foamix Pharmaceuticals Ltd. Carriers, formulations, methods for formulating unstable active agents for external application and uses thereof
US9795564B2 (en) 2007-12-07 2017-10-24 Foamix Pharmaceuticals Ltd. Oil-based foamable carriers and formulations
US8343945B2 (en) 2007-12-07 2013-01-01 Foamix Ltd. Carriers, formulations, methods for formulating unstable active agents for external application and uses thereof
US11433025B2 (en) 2007-12-07 2022-09-06 Vyne Therapeutics Inc. Oil foamable carriers and formulations
US8900553B2 (en) 2007-12-07 2014-12-02 Foamix Pharmaceuticals Ltd. Oil and liquid silicone foamable carriers and formulations
US8709385B2 (en) 2008-01-14 2014-04-29 Foamix Ltd. Poloxamer foamable pharmaceutical compositions with active agents and/or therapeutic cells and uses
US10588858B2 (en) 2009-04-28 2020-03-17 Foamix Pharmaceuticals Ltd. Foamable vehicles and pharmaceutical compositions comprising aprotic polar solvents and uses thereof
US10363216B2 (en) 2009-04-28 2019-07-30 Foamix Pharmaceuticals Ltd. Foamable vehicles and pharmaceutical compositions comprising aprotic polar solvents and uses thereof
US9884017B2 (en) 2009-04-28 2018-02-06 Foamix Pharmaceuticals Ltd. Foamable vehicles and pharmaceutical compositions comprising aprotic polar solvents and uses thereof
US10213384B2 (en) 2009-04-28 2019-02-26 Foamix Pharmaceuticals Ltd. Foamable vehicles and pharmaceutical compositions comprising aprotic polar solvents and uses thereof
US11219631B2 (en) 2009-07-29 2022-01-11 Vyne Pharmaceuticals Inc. Foamable compositions, breakable foams and their uses
US9572775B2 (en) 2009-07-29 2017-02-21 Foamix Pharmaceuticals Ltd. Non surfactant hydro-alcoholic foamable compositions, breakable foams and their uses
US10092588B2 (en) 2009-07-29 2018-10-09 Foamix Pharmaceuticals Ltd. Foamable compositions, breakable foams and their uses
US9167813B2 (en) 2009-07-29 2015-10-27 Foamix Pharmaceuticals Ltd. Non surfactant hydro-alcoholic foamable compositions, breakable foams and their uses
US9072667B2 (en) 2009-07-29 2015-07-07 Foamix Pharmaceuticals Ltd. Non surface active agent non polymeric agent hydro-alcoholic foamable compositions, breakable foams and their uses
US10350166B2 (en) 2009-07-29 2019-07-16 Foamix Pharmaceuticals Ltd. Non surface active agent non polymeric agent hydro-alcoholic foamable compositions, breakable foams and their uses
US10610599B2 (en) 2009-10-02 2020-04-07 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US8992896B2 (en) 2009-10-02 2015-03-31 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US10967063B2 (en) 2009-10-02 2021-04-06 Vyne Therapeutics Inc. Surfactant-free, water-free formable composition and breakable foams and their uses
US10137200B2 (en) 2009-10-02 2018-11-27 Foamix Pharmaceuticals Ltd. Surfactant-free water-free foamable compositions, breakable foams and gels and their uses
US10213512B2 (en) 2009-10-02 2019-02-26 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US10029013B2 (en) 2009-10-02 2018-07-24 Foamix Pharmaceuticals Ltd. Surfactant-free, water-free formable composition and breakable foams and their uses
US10238746B2 (en) 2009-10-02 2019-03-26 Foamix Pharmaceuticals Ltd Surfactant-free water-free foamable compositions, breakable foams and gels and their uses
US10265404B2 (en) 2009-10-02 2019-04-23 Foamix Pharmaceuticals Ltd. Compositions, gels and foams with rheology modulators and uses thereof
US10086080B2 (en) 2009-10-02 2018-10-02 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US10835613B2 (en) 2009-10-02 2020-11-17 Foamix Pharmaceuticals Ltd. Compositions, gels and foams with rheology modulators and uses thereof
US10322186B2 (en) 2009-10-02 2019-06-18 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US10946101B2 (en) 2009-10-02 2021-03-16 Vyne Therapeutics Inc. Surfactant-free water-free foamable compositions, breakable foams and gels and their uses
US9849142B2 (en) 2009-10-02 2017-12-26 Foamix Pharmaceuticals Ltd. Methods for accelerated return of skin integrity and for the treatment of impetigo
US10821187B2 (en) 2009-10-02 2020-11-03 Foamix Pharmaceuticals Ltd. Compositions, gels and foams with rheology modulators and uses thereof
US8945516B2 (en) 2009-10-02 2015-02-03 Foamix Pharmaceuticals Ltd. Surfactant-free water-free foamable compositions, breakable foams and gels and their uses
US8871184B2 (en) 2009-10-02 2014-10-28 Foamix Ltd. Topical tetracycline compositions
US10463742B2 (en) 2009-10-02 2019-11-05 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US10517882B2 (en) 2009-10-02 2019-12-31 Foamix Pharmaceuticals Ltd. Method for healing of an infected acne lesion without scarring
US9675700B2 (en) 2009-10-02 2017-06-13 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US8865139B1 (en) 2009-10-02 2014-10-21 Foamix Pharmaceuticals Ltd. Topical tetracycline compositions
US8618081B2 (en) 2009-10-02 2013-12-31 Foamix Ltd. Compositions, gels and foams with rheology modulators and uses thereof
US9812179B2 (en) 2009-11-24 2017-11-07 Ovonyx Memory Technology, Llc Techniques for reducing disturbance in a semiconductor memory device
US8760906B2 (en) 2009-11-24 2014-06-24 Micron Technology, Inc. Techniques for reducing disturbance in a semiconductor memory device
US20140221320A1 (en) * 2011-07-08 2014-08-07 The Research Foundation For The State University Of New York Topical minocycline ointment for suppression of allergic skin responses
US10272098B2 (en) 2013-03-14 2019-04-30 Drexel University Chelated drug delivery systems
WO2014152790A1 (en) * 2013-03-14 2014-09-25 Drexel University Chelated drug delivery systems
US10881672B2 (en) 2015-03-23 2021-01-05 BioPharmX, Inc. Pharmaceutical tetracycline composition for dermatological use
US10391108B2 (en) 2015-03-23 2019-08-27 BioPharmX, Inc. Pharmaceutical tetracycline composition for dermatological use
US9918998B2 (en) 2015-03-23 2018-03-20 BioPharmX, Inc. Pharmaceutical tetracycline composition for dermatological use
US10849847B2 (en) 2016-09-08 2020-12-01 Foamix Pharamaceuticals Ltd. Compositions and methods for treating rosacea and acne
US10398641B2 (en) 2016-09-08 2019-09-03 Foamix Pharmaceuticals Ltd. Compositions and methods for treating rosacea and acne
US11324691B2 (en) 2016-09-08 2022-05-10 Journey Medical Corporation Compositions and methods for treating rosacea and acne

Also Published As

Publication number Publication date
JP4653282B2 (en) 2011-03-16
US20020002151A1 (en) 2002-01-03
KR20010107662A (en) 2001-12-07
TWI285551B (en) 2007-08-21
KR100884575B1 (en) 2009-02-19
JP2001335477A (en) 2001-12-04

Similar Documents

Publication Publication Date Title
US6566350B2 (en) Minocycline-containing compositions
US4701320A (en) Composition stably containing minocycline for treating periodontal diseases
JPH11503160A (en) Pharmaceutical composition containing proton pump inhibitor
HU230300B1 (en) Topical compositions for prostaglandin e1 delivery
JP7091477B2 (en) Edaravone pharmaceutical composition
JP4195178B2 (en) Anti-inflammatory analgesic topical
WO1998041210A1 (en) Sustained-release prostaglandin i derivative preparation
JP2019006736A (en) Pharmaceutical composition
AU2003240164A1 (en) Extended release formulation of divalproex sodium
JPH07267839A (en) Ointment composition adhesive to oral mucosa
JPH0617300B2 (en) Composition for treating periodontal disease
JP2001233766A (en) Pravastatin sodium tablet
US4965262A (en) Method for treating or preventing locally periodontal disease
JPH11286448A (en) Composition containing minocycline
JP6908449B2 (en) Pharmaceutical composition
JP2021042197A (en) Oral composition
JP2006182699A (en) Composition for oral cavity
JP2003160500A (en) Popidone iodine-containing composition
JPH0234325B2 (en) SHISHUSHITSUKANCHIRYOYOSOSEIBUTSU
JPH0371409B2 (en)
JP2928261B2 (en) Method for producing stable polyprenyl compound-containing composition
FR2635463A1 (en) PHARMACEUTICAL COMPOSITION COMPRISING A ACTIVE INGREDIENTLY WATER-SOLUBLE PRINCIPLE AND AT LEAST ONE GLYCERIDE GELIFIED BY AT LEAST ONE CELLULOSIC POLYMER
JP5130601B2 (en) Semi-solid oral composition
JP3331236B2 (en) Oral composition
JP2019006737A (en) Pharmaceutical composition

Legal Events

Date Code Title Description
AS Assignment

Owner name: SHOWA YAKUHIN KAKO CO., LTD., JAPAN

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:ONO, KAZUHIRO;SAKAGUCHI, HIDENARI;HAYAKAWA, IKUTO;REEL/FRAME:012091/0324

Effective date: 20010810

STCF Information on status: patent grant

Free format text: PATENTED CASE

CC Certificate of correction
FPAY Fee payment

Year of fee payment: 4

FPAY Fee payment

Year of fee payment: 8

FPAY Fee payment

Year of fee payment: 12

AS Assignment

Owner name: SHOWA YAKUHIN KAKO CO., LTD., JAPAN

Free format text: CHANGE OF ADDRESS;ASSIGNOR:SHOWA YAKUHIN KAKO CO., LTD.;REEL/FRAME:036313/0949

Effective date: 20010810